To evaluate and map research examining clinical associations with the Duffy-null variant.

Scoping review of the existing literature.

We conducted a systematic search of PubMed, Embase, CINAHL and Web of Science for studies published in English between 1 January 2000 and 25 June 2024.

Studies were eligible for inclusion if they examined associations relevant to current standard clinical practice and met our protocol’s inclusion criteria.

We extracted the following information from included studies: study year(s), patient population, sample size, study design, primary outcome and primary findings. Studies were grouped by outcome and synthesised in tabular and qualitative formats.

A total of 2737 studies were screened, and 44 met our inclusion criteria. Most studies were observational, and the most common research question examined was the association with resistance to Plasmodium vivax malaria (9/44). Overall, we observed that the association between the Duffy-null variant and asymptomatic lower absolute neutrophil count (ANC) is demonstrated in large prospective cohort studies. The association with resistance to P. vivax malaria is primarily supported by large cross-sectional studies. There were no studies examining the practical applications of these findings, for example, optimal Duffy-genotype adjusted ANC thresholds for clinical decision-making in patients receiving chemotherapy. Finally, we observed that 19 different associations with this trait have been explored, several in conditions with no clear link to the Duffy trait, for example, progression rates in HIV/AIDS, risk of diabetes, etc.

We found established associations between the Duffy-null variant and asymptomatic lower ANC and with resistance to P. vivax malaria but a lack of data for the practical utilisation of these findings in clinical care. Future studies, such as those examining safe ANC values for entry into clinical trials and for ANC nadir for Duffy-null patients receiving medications associated with increased risk of neutropenia, for example, clozapine, are needed. We observed numerous reported associations of unclear clinical utility. Studies investigating associations with the Duffy trait should be guided by biologic plausibility and clinical utility of positive findings.